Estimates of Bivalent mRNA Vaccine Durability in Preventing COVID-19-Associated Hospitalization and Critical Illness Among Adults with and Without Immunocompromising Conditions - VISION Network, September 2022-April 2023.

On September 1, 2022, CDC's Advisory Committee on Immunization Practices (ACIP) recommended a single bivalent mRNA COVID-19 booster dose for persons aged ≥12 years who had completed at least a monovalent primary series. Early vaccine effectiveness (VE) estimates among adults aged ≥18 years showed receipt of a bivalent booster dose provided additional protection against COVID-19-associated emergency department and urgent care visits and hospitalizations compared with that in persons who had received only monovalent vaccine doses (1); however, insufficient time had elapsed since bivalent vaccine authorization to assess the durability of this protection. The VISION Network* assessed VE against COVID-19-associated hospitalizations by time since bivalent vaccine receipt during September 13, 2022-April 21, 2023, among adults aged ≥18 years with and without immunocompromising conditions. During the first 7-59 days after vaccination, compared with no vaccination, VE for receipt of a bivalent vaccine dose among adults aged ≥18 years was 62% (95% CI = 57%-67%) among adults without immunocompromising conditions and 28% (95% CI = 10%-42%) among adults with immunocompromising conditions. Among adults without immunocompromising conditions, VE declined to 24% (95% CI = 12%-33%) among those aged ≥18 years by 120-179 days after vaccination. VE was generally lower for adults with immunocompromising conditions. A bivalent booster dose provided the highest protection, and protection was sustained through at least 179 days against critical outcomes, including intensive care unit (ICU) admission or in-hospital death. These data support updated recommendations allowing additional optional bivalent COVID-19 vaccine doses for certain high-risk populations. All eligible persons should stay up to date with recommended COVID-19 vaccines.

Effectiveness of COVID-19 Vaccines at Preventing Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompromised Adults: An Observational Study of Real-World Data Across 10 US States from August-December 2021

Background Immunocompromised (IC) persons are at increased risk for severe COVID-19 outcomes and are less protected by 1-2 COVID-19 vaccine doses than are immunocompetent (non-IC) persons. We compared vaccine effectiveness (VE) against medically attended COVID-19 of 2-3 mRNA and 1-2 viral-vector vaccine doses between IC and non-IC adults. Methods Using a test-negative design among eight VISION Network sites, VE against laboratory-confirmed COVID-19–associated emergency department (ED) or urgent care (UC) events and hospitalizations from 26 August-25 December 2021 was estimated separately among IC and non-IC adults and among specific IC condition subgroups. Vaccination status was defined using number and timing of doses. VE for each status (versus unvaccinated) was adjusted for age, geography, time, prior positive test result, and local SARS-CoV-2 circulation. Results We analyzed 8,848 ED/UC events and 18,843 hospitalizations among IC patients and 200,071 ED/UC events and 70,882 hospitalizations among non-IC patients. Among IC patients, 3-dose mRNA VE against ED/UC (73% [95% CI: 64-80]) and hospitalization (81% [95% CI: 76-86]) was lower than that among non-IC patients (ED/UC: 94% [95% CI: 93-94];hospitalization: 96% [95% CI: 95-97]). Similar patterns were observed for viral-vector vaccines. Transplant recipients had lower VE than other IC subgroups. Conclusions During B.1.617.2 (Delta) variant predominance, IC adults received moderate protection against COVID-19–associated medical events from three mRNA doses, or one viral-vector dose plus a second dose of any product. However, protection was lower in IC versus non-IC patients, especially among transplant recipients, underscoring the need for additional protection among IC adults.

Effectiveness of BNT162b2 COVID-19 Vaccination in Children and Adolescents.

OBJECTIVES: We assessed BNT162b2 vaccine effectiveness (VE) against mild to moderate and severe coronavirus disease 2019 (COVID-19) in children and adolescents through the Omicron BA.4/BA.5 period. METHODS: Using VISION Network records from April 2021 to September 2022, we conducted a test-negative, case-control study assessing VE against COVID-19-associated emergency department/urgent care (ED/UC) encounters and hospitalizations using logistic regression, conditioned on month and site, adjusted for covariates. RESULTS: We compared 9800 ED/UC cases with 70 232 controls, and 305 hospitalized cases with 2612 controls. During Delta, 2-dose VE against ED/UC encounters at 12 to 15 years was initially 93% (95% confidence interval 89 to 95), waning to 77% (69% to 84%) after ≥150 days. At ages 16 to 17, VE was initially 93% (86% to 97%), waning to 72% (63% to 79%) after ≥150 days. During Omicron, VE at ages 12 to 15 was initially 64% (44% to 77%), waning to 13% (3% to 23%) after ≥150 days; at ages 16 to 17 VE was 31% (10% to 47%) during days 60 to 149, waning to 7% (-8 to 20%) after 150 days. A monovalent booster increased VE to 54% (40% to 65%) at ages 12 to 15 and 46% (30% to 58%) at ages 16 to 17. At ages 5 to 11, 2-dose VE was 49% (33% to 61%) initially and 41% (29% to 51%) after 150 days. During Delta, VE against hospitalizations at ages 12 to 17 was high (>97%), and at ages 16 to 17 remained 98% (73% to 100%) beyond 150 days; during Omicron, hospitalizations were too infrequent to precisely estimate VE. CONCLUSIONS: BNT162b2 protected children and adolescents against mild to moderate and severe COVID-19. VE was lower during Omicron predominance including BA.4/BA.5, waned after dose 2 but increased after a monovalent booster. Children and adolescents should receive all recommended COVID-19 vaccinations.

Protection of 2 and 3 mRNA Vaccine Doses Against Severe Outcomes Among Adults Hospitalized with COVID-19 - VISION Network, August 2021 - March 2022.

BACKGROUND: We assessed COVID-19 vaccination impact on illness severity among adults hospitalized with COVID-19 August 2021-March 2022. METHODS: We evaluated differences in intensive care unit (ICU) admission, in-hospital death, and length of stay among vaccinated (2 or 3 mRNA vaccine doses) versus unvaccinated patients aged ≥18 years hospitalized for ≥24 hours with COVID-19-like illness (CLI) and positive SARS-CoV-2 molecular testing. We calculated odds ratios for ICU admission and death and subdistribution hazard ratios (SHR) for time to hospital discharge adjusted for age, geographic region, calendar time, and local virus circulation. RESULTS: We included 27,149 SARS-CoV-2 positive hospitalizations. During both Delta and Omicron-predominant periods, protection against ICU admission was strongest among 3-dose vaccinees compared with unvaccinated patients (Delta OR [CI]: 0.52 [0.28-0.96]); Omicron OR [CI]: 0.69 [0.54-0.87]). During both periods, risk of in-hospital of death was lower among vaccinated compared with unvaccinated but ORs were overlapping; during Omicron, lowest among 3-dose vaccinees (OR [CI] 0.39 [0.28-0.54]). We observed SHR >1 across all vaccination strata in both periods indicating faster discharge for vaccinated patients. CONCLUSIONS: COVID-19 vaccination was associated with lower rates of ICU admission and in-hospital death in both Delta and Omicron periods compared with being unvaccinated.

Maternal SARS-CoV-2 vaccination and infant protection against SARS-CoV-2 during the first six months of life.

We examined the effectiveness of maternal vaccination against SARS-CoV-2 infection in 30,311 infants born at Kaiser Permanente Northern California from December 15, 2020, to May 31, 2022. Using Cox regression, the effectiveness of ≥2 doses of COVID-19 vaccine received during pregnancy was 84% (95% confidence interval [CI]: 66, 93), 62% (CI: 39, 77) and 56% (CI: 34,71) during months 0-2, 0-4 and 0- 6 of a child's life, respectively, in the Delta variant period. In the Omicron variant period, the effectiveness of maternal vaccination in these three age intervals was 21% (CI: -21,48), 14% (CI: -9,32) and 13% (CI: -3,26), respectively. Over the entire study period, the incidence of hospitalization for COVID-19 was lower during the first 6 months of life among infants of vaccinated mothers compared with infants of unvaccinated mothers (21/100,000 person-years vs. 100/100,000 person-years). Maternal vaccination was protective, but protection was lower during Omicron than during Delta. Protection during both periods decreased as infants aged.

Estimation of COVID-19 mRNA Vaccine Effectiveness and COVID-19 Illness and Severity by Vaccination Status During Omicron BA.4 and BA.5 Sublineage Periods.

Importance: Recent SARS-CoV-2 Omicron variant sublineages, including BA.4 and BA.5, may be associated with greater immune evasion and less protection against COVID-19 after vaccination. Objectives: To evaluate the estimated vaccine effectiveness (VE) of 2, 3, or 4 doses of COVID-19 mRNA vaccination among immunocompetent adults during a period of BA.4 or BA.5 predominant circulation; and to evaluate the relative severity of COVID-19 in hospitalized patients across Omicron BA.1, BA.2 or BA.2.12.1, and BA.4 or BA.5 sublineage periods. Design, Setting, and Participants: This test-negative case-control study was conducted in 10 states with data from emergency department (ED) and urgent care (UC) encounters and hospitalizations from December 16, 2021, to August 20, 2022. Participants included adults with COVID-19-like illness and molecular testing for SARS-CoV-2. Data were analyzed from August 2 to September 21, 2022. Exposures: mRNA COVID-19 vaccination. Main Outcomes and Measures: The outcomes of interest were COVID-19 ED or UC encounters, hospitalizations, and admission to the intensive care unit (ICU) or in-hospital death. VE associated with protection against medically attended COVID-19 was estimated, stratified by care setting and vaccine doses (2, 3, or 4 doses vs 0 doses as the reference group). Among hospitalized patients with COVID-19, demographic and clinical characteristics and in-hospital outcomes were compared across sublineage periods. Results: During the BA.4 and BA.5 predominant period, there were 82 229 eligible ED and UC encounters among patients with COVID-19-like illness (median [IQR] age, 51 [33-70] years; 49 682 [60.4%] female patients), and 19 114 patients (23.2%) had test results positive for SARS-CoV-2; among 21 007 hospitalized patients (median [IQR] age, 71 [58-81] years; 11 209 [53.4%] female patients), 3583 (17.1 %) had test results positive for SARS-CoV-2. Estimated VE against hospitalization was 25% (95% CI, 17%-32%) for receipt of 2 vaccine doses at 150 days or more after receipt, 68% (95% CI, 50%-80%) for a third dose 7 to 119 days after receipt, and 36% (95% CI, 29%-42%) for a third dose 120 days or more (median [IQR], 235 [204-262] days) after receipt. Among patients aged 65 years or older who had received a fourth vaccine dose, VE was 66% (95% CI, 53%-75%) at 7 to 59 days after vaccination and 57% (95% CI, 44%-66%) at 60 days or more (median [IQR], 88 [75-105] days) after vaccination. Among hospitalized patients with COVID-19, ICU admission or in-hospital death occurred in 21.4% of patients during the BA.1 period vs 14.7% during the BA.4 and BA.5 period (standardized mean difference: 0.17). Conclusions and Relevance: In this case-control study of COVID-19 vaccines and illness, VE associated with protection against medically attended COVID-19 illness was lower with increasing time since last dose; estimated VE was higher after receipt of 1 or 2 booster doses compared with a primary series alone.

Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults - VISION Network, Nine States, September-November 2022.

During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness.† VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 32% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 59% compared with no vaccination, 42% compared with monovalent vaccination only with last dose 5-7 months earlier, and 48% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high.

Vaccine Effectiveness Against Influenza-Associated Urgent Care, Emergency Department, and Hospital Encounters During the 2021-2022 Season, VISION Network.

BACKGROUND: Following historically low influenza activity during the 2020-2021 season, the United States saw an increase in influenza circulating during the 2021-2022 season. Most viruses belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade. METHODS: We conducted a test-negative case-control analysis among adults ≥18 years of age at 3 sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders. RESULTS: In total, 86 732 ED/UC ARI-associated encounters (7696 [9%] cases) and 16 805 hospitalized ARI-associated encounters (649 [4%] cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI), 20%-29%) and 25% (95% CI, 11%-37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; 95% CI, -5% to 17%) or with immunocompromising conditions (4%; 95% CI, -45% to 36%). CONCLUSIONS: During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE.

Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults - VISION Network, Nine States, September-November 2022.

During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness.† VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 31% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 57% compared with no vaccination, 38% compared with monovalent vaccination only with last dose 5-7 months earlier, and 45% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high.

Effectiveness of COVID-19 mRNA Vaccines Against COVID-19-Associated Hospitalizations Among Immunocompromised Adults During SARS-CoV-2 Omicron Predominance - VISION Network, 10 States, December 2021-August 2022.

Persons with moderate-to-severe immunocompromising conditions might have reduced protection after COVID-19 vaccination, compared with persons without immunocompromising conditions (1-3). On August 13, 2021, the Advisory Committee on Immunization Practices (ACIP) recommended that adults with immunocompromising conditions receive an expanded primary series of 3 doses of an mRNA COVID-19 vaccine. ACIP followed with recommendations on September 23, 2021, for a fourth (booster) dose and on September 1, 2022, for a new bivalent mRNA COVID-19 vaccine booster dose, containing components of the BA.4 and BA.5 sublineages of the Omicron (B.1.1.529) variant (4). Data on vaccine effectiveness (VE) of monovalent COVID-19 vaccines among persons with immunocompromising conditions since the emergence of the Omicron variant in December 2021 are limited. In the multistate VISION Network,§ monovalent 2-, 3-, and 4-dose mRNA VE against COVID-19-related hospitalization were estimated among adults with immunocompromising conditions¶ hospitalized with COVID-19-like illness,** using a test-negative design comparing odds of previous vaccination among persons with a positive or negative molecular test result (case-patients and control-patients) for SARS-CoV-2 (the virus that causes COVID-19). During December 16, 2021-August 20, 2022, among SARS-CoV-2 test-positive case-patients, 1,815 (36.3%), 1,387 (27.7%), 1,552 (31.0%), and 251 (5.0%) received 0, 2, 3, and 4 mRNA COVID-19 vaccine doses, respectively. Among test-negative control-patients during this period, 6,928 (23.7%), 7,411 (25.4%), 12,734 (43.6%), and 2,142 (7.3%) received these respective doses. Overall, VE against COVID-19-related hospitalization among adults with immunocompromising conditions hospitalized for COVID-like illness during Omicron predominance was 36% ≥14 days after dose 2, 69% 7-89 days after dose 3, and 44% ≥90 days after dose 3. Restricting the analysis to later periods when Omicron sublineages BA.2/BA.2.12.1 and BA.4/BA.5 were predominant and 3-dose recipients were eligible to receive a fourth dose, VE was 32% ≥90 days after dose 3 and 43% ≥7 days after dose 4. Protection offered by vaccination among persons with immunocompromising conditions during Omicron predominance was moderate even after a 3-dose monovalent primary series or booster dose. Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP recommendations. Further, additional protective recommendations for persons with immunocompromising conditions, including the use of prophylactic antibody therapy, early access to and use of antivirals, and enhanced nonpharmaceutical interventions such as well-fitting masks or respirators, should also be considered.

Waning of vaccine effectiveness against moderate and severe covid-19 among adults in the US from the VISION network: test negative, case-control study.

OBJECTIVE: To estimate the effectiveness of mRNA vaccines against moderate and severe covid-19 in adults by time since second, third, or fourth doses, and by age and immunocompromised status. DESIGN: Test negative case-control study. SETTING: Hospitals, emergency departments, and urgent care clinics in 10 US states, 17 January 2021 to 12 July 2022. PARTICIPANTS: 893 461 adults (≥18 years) admitted to one of 261 hospitals or to one of 272 emergency department or 119 urgent care centers for covid-like illness tested for SARS-CoV-2. MAIN OUTCOME MEASURES: The main outcome was waning of vaccine effectiveness with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine during the omicron and delta periods, and the period before delta was dominant using logistic regression conditioned on calendar week and geographic area while adjusting for age, race, ethnicity, local virus circulation, immunocompromised status, and likelihood of being vaccinated. RESULTS: 45 903 people admitted to hospital with covid-19 (cases) were compared with 213 103 people with covid-like illness who tested negative for SARS-CoV-2 (controls), and 103 287 people admitted to emergency department or urgent care with covid-19 (cases) were compared with 531 168 people with covid-like illness who tested negative for SARS-CoV-2. In the omicron period, vaccine effectiveness against covid-19 requiring admission to hospital was 89% (95% confidence interval 88% to 90%) within two months after dose 3 but waned to 66% (63% to 68%) by four to five months. Vaccine effectiveness of three doses against emergency department or urgent care visits was 83% (82% to 84%) initially but waned to 46% (44% to 49%) by four to five months. Waning was evident in all subgroups, including young adults and individuals who were not immunocompromised; although waning was morein people who were immunocompromised. Vaccine effectiveness increased among most groups after a fourth dose in whom this booster was recommended. CONCLUSIONS: Effectiveness of mRNA vaccines against moderate and severe covid-19 waned with time after vaccination. The findings support recommendations for a booster dose after a primary series and consideration of additional booster doses.

Estimation of COVID-19 mRNA Vaccine Effectiveness Against Medically Attended COVID-19 in Pregnancy During Periods of Delta and Omicron Variant Predominance in the United States.

Importance: Pregnant people are at high risk for severe COVID-19 but were excluded from mRNA vaccine trials; data on COVID-19 vaccine effectiveness (VE) are needed. Objective: To evaluate the estimated effectiveness of mRNA vaccination against medically attended COVID-19 among pregnant people during Delta and Omicron predominance. Design, Setting, and Participants: This test-negative, case-control study was conducted from June 2021 to June 2022 in a network of 306 hospitals and 164 emergency department and urgent care (ED/UC) facilities across 10 US states, including 4517 ED/UC encounters and 975 hospitalizations among pregnant people with COVID-19-like illness (CLI) who underwent SARS-CoV-2 molecular testing. Exposures: Two doses (14-149 and ≥150 days prior) and 3 doses (7-119 and ≥120 days prior) of COVID-19 mRNA vaccine (≥1 dose received during pregnancy) vs unvaccinated. Main Outcomes and Measures: Estimated VE against laboratory-confirmed COVID-19-associated ED/UC encounter or hospitalization, based on the adjusted odds ratio (aOR) for prior vaccination; VE was calculated as (1 - aOR) × 100%. Results: Among 4517 eligible CLI-associated ED/UC encounters and 975 hospitalizations, 885 (19.6%) and 334 (34.3%) were SARS-CoV-2 positive, respectively; the median (IQR) patient age was 28 (24-32) years and 31 (26-35) years, 537 (12.0%) and 118 (12.0%) were non-Hispanic Black and 1189 (26.0%) and 240 (25.0%) were Hispanic. During Delta predominance, the estimated VE against COVID-19-associated ED/UC encounters was 84% (95% CI, 69% to 92%) for 2 doses within 14 to 149 days, 75% (95% CI, 5% to 93%) for 2 doses 150 or more days prior, and 81% (95% CI, 30% to 95%) for 3 doses 7 to 119 days prior; estimated VE against COVID-19-associated hospitalization was 99% (95% CI, 96% to 100%), 96% (95% CI, 86% to 99%), and 97% (95% CI, 79% to 100%), respectively. During Omicron predominance, for ED/UC encounters, the estimated VE of 2 doses within 14 to 149 days, 2 doses 150 or more days, 3 doses within 7 to 119 days, and 3 doses 120 or more days prior was 3% (95% CI, -49% to 37%), 42% (95% CI, -16% to 72%), 79% (95% CI, 59% to 89%), and -124% (95% CI, -414% to 2%), respectively; for hospitalization, estimated VE was 86% (95% CI, 41% to 97%), 64% (95% CI, -102% to 93%), 86% (95% CI, 28% to 97%), and -53% (95% CI, -1254% to 83%), respectively. Conclusions and Relevance: In this study, maternal mRNA COVID-19 vaccination, including booster dose, was associated with protection against medically attended COVID-19. VE estimates were higher against COVID-19-associated hospitalization than ED/UC visits and lower against the Omicron variant than the Delta variant. Protection waned over time, particularly during Omicron predominance.

Safety of COVID-19 Vaccination in United States Children Ages 5 to 11 Years.

BACKGROUND AND OBJECTIVES: Limited postauthorization safety data for the Pfizer-BioNTech coronavirus disease 2019 vaccination among children ages 5 to 11 years are available, particularly for the adverse event myocarditis, which has been detected in adolescents and young adults. We describe adverse events observed during the first 4 months of the United States coronavirus disease 2019 vaccination program in this age group. METHODS: We analyzed data from 3 United States safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health effects; the Vaccine Adverse Events Reporting System (VAERS), the national spontaneous reporting system comanaged by the Centers for Disease Control and Prevention and Food and Drug Administration; and the Vaccine Safety Datalink, an active surveillance system that monitors electronic health records for prespecified events, including myocarditis. RESULTS: Among 48 795 children ages 5 to 11 years enrolled in v-safe, most reported reactions were mild-to-moderate, most frequently reported the day after vaccination, and were more common after dose 2. VAERS received 7578 adverse event reports; 97% were nonserious. On review of 194 serious VAERS reports, 15 myocarditis cases were verified; 8 occurred in boys after dose 2 (reporting rate 2.2 per million doses). In the Vaccine Safety Datalink, no safety signals were detected in weekly sequential monitoring after administration of 726 820 doses. CONCLUSIONS: Safety findings for Pfizer-BioNTech vaccine from 3 United States monitoring systems in children ages 5 to 11 years show that most reported adverse events were mild and no safety signals were observed in active surveillance. VAERS reporting rates of myocarditis after dose 2 in this age group were substantially lower than those observed among adolescents ages 12 to 15 years.

Effectiveness of 2, 3, and 4 COVID-19 mRNA Vaccine Doses Among Immunocompetent Adults During Periods when SARS-CoV-2 Omicron BA.1 and BA.2/BA.2.12.1 Sublineages Predominated - VISION Network, 10 States, December 2021-June 2022.

The Omicron variant (B.1.1.529) of SARS-CoV-2, the virus that causes COVID-19, was first identified in the United States in November 2021, with the BA.1 sublineage (including BA.1.1) causing the largest surge in COVID-19 cases to date. Omicron sublineages BA.2 and BA.2.12.1 emerged later and by late April 2022, accounted for most cases.* Estimates of COVID-19 vaccine effectiveness (VE) can be reduced by newly emerging variants or sublineages that evade vaccine-induced immunity (1), protection from previous SARS-CoV-2 infection in unvaccinated persons (2), or increasing time since vaccination (3). Real-world data comparing VE during the periods when the BA.1 and BA.2/BA.2.12.1 predominated (BA.1 period and BA.2/BA.2.12.1 period, respectively) are limited. The VISION network† examined 214,487 emergency department/urgent care (ED/UC) visits and 58,782 hospitalizations with a COVID-19-like illness§ diagnosis among 10 states during December 18, 2021-June 10, 2022, to evaluate VE of 2, 3, and 4 doses of mRNA COVID-19 vaccines (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) compared with no vaccination among adults without immunocompromising conditions. VE against COVID-19-associated hospitalization 7-119 days and ≥120 days after receipt of dose 3 was 92% (95% CI = 91%-93%) and 85% (95% CI = 81%-89%), respectively, during the BA.1 period, compared with 69% (95% CI = 58%-76%) and 52% (95% CI = 44%-59%), respectively, during the BA.2/BA.2.12.1 period. Patterns were similar for ED/UC encounters. Among adults aged ≥50 years, VE against COVID-19-associated hospitalization ≥120 days after receipt of dose 3 was 55% (95% CI = 46%-62%) and ≥7 days (median = 27 days) after a fourth dose was 80% (95% CI = 71%-85%) during BA.2/BA.2.12.1 predominance. Immunocompetent persons should receive recommended COVID-19 booster doses to prevent moderate to severe COVID-19, including a first booster dose for all eligible persons and second booster dose for adults aged ≥50 years at least 4 months after an initial booster dose. Booster doses should be obtained immediately when persons become eligible.¶.

Risk of myocarditis and pericarditis following BNT162b2 and mRNA-1273 COVID-19 vaccination.

BACKGROUND: Evidence indicates that mRNA COVID-19 vaccination is associated with risk of myocarditis and possibly pericarditis, especially in young males. It is not clear if risk differs between mRNA-1273 versus BNT162b2. We assessed if risk differs using comprehensive health records on a diverse population. METHODS: Members 18-39 years of age at eight integrated healthcare-delivery systems were monitored using data updated weekly and supplemented with medical record review of myocarditis and pericarditis cases. Incidence of myocarditis and pericarditis events that occurred among vaccine recipients 0 to 7 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by conditional Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. Head-to-head comparison directly assessed risk following mRNA-1273 versus BNT162b2 during 0-7 days post-vaccination. RESULTS: From December 14, 2020 - January 15, 2022 there were 41 cases after 2,891,498 doses of BNT162b2 and 38 cases after 1,803,267 doses of mRNA-1273. Cases had similar demographic and clinical characteristics. Most were hospitalized for ≤1 day; none required intensive care. During days 0-7 after dose 2 of BNT162b2, the incidence was 14.3 (CI: 6.5-34.9) times higher than the comparison interval, amounting to 22.4 excess cases per million doses; after mRNA-1273 the incidence was 18.8 (CI: 6.7-64.9) times higher than the comparison interval, amounting to 31.2 excess cases per million doses. In head-to-head comparisons 0-7 days after either dose, risk was moderately higher after mRNA-1273 than after BNT162b2 (RR: 1.61, CI 1.02-2.54). CONCLUSIONS: Both vaccines were associated with increased risk of myocarditis and pericarditis in 18-39-year-olds. Risk estimates were modestly higher after mRNA-1273 than after BNT162b2.

Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink.

Importance: Postauthorization monitoring of vaccines in a large population may detect rare adverse events not identified in clinical trials such as Guillain-Barré syndrome (GBS), which has a background rate of 1 to 2 per 100 000 person-years. Objective: To describe cases and incidence of GBS following COVID-19 vaccination and assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines. Design, Setting, and Participants: This cohort study used surveillance data from the Vaccine Safety Datalink at 8 participating integrated health care systems in the United States. There were 10 158 003 participants aged at least 12 years. Data analysis was performed from November 2021 to February 2022. Exposures: Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine, including mRNA vaccine doses 1 and 2, December 13, 2020, to November 13, 2021. Main Outcomes and Measures: GBS with symptom onset in the 1 to 84 days after vaccination, confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared with the background rate, rate ratios (RRs) comparing GBS incidence in the 1 to 21 vs 22 to 42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs mRNA vaccination, using Poisson regression adjusted for age, sex, race and ethnicity, site, and calendar day. Results: From December 13, 2020, through November 13, 2021, 15 120 073 doses of COVID-19 vaccines were administered to 7 894 989 individuals (mean [SE] age, 46.5 [0.02] years; 8 138 318 doses received [53.8%] by female individuals; 3 671 199 doses received [24.3%] by Hispanic or Latino individuals, 2 215 064 doses received [14.7%] by Asian individuals, 6 266 424 doses received [41.4%] by White individuals), including 483 053 Ad.26.COV2.S doses, 8 806 595 BNT162b2 doses, and 5 830 425 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of GBS per 100 000 person-years in the 1 to 21 days after Ad.26.COV2.S was 32.4 (95% CI, 14.8-61.5), significantly higher than the background rate, and the adjusted RR in the 1 to 21 vs 22 to 42 days following Ad.26.COV2.S was 6.03 (95% CI, 0.79-147.79). Thirty-six cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate per 100 000 person-years in the 1 to 21 days after mRNA vaccines was 1.3 (95% CI, 0.7-2.4) and the adjusted RR in the 1 to 21 vs 22 to 42 days following mRNA vaccines was 0.56 (95% CI, 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs mRNA vaccines, the adjusted RR was 20.56 (95% CI, 6.94-64.66). Conclusions and Relevance: In this cohort study of COVID-19 vaccines, the incidence of GBS was elevated after receiving the Ad.26.COV2.S vaccine. Surveillance is ongoing.

Dashboard development for near real-time visualization of COVID-19 vaccine safety surveillance data in the vaccine safety datalink.

The Vaccine Safety Datalink (VSD) conducts active surveillance and vaccine safety research studies. Since the start of the U.S. COVID-19 vaccination program, the VSD has conducted near real-time safety surveillance of COVID-19 vaccines using Rapid Cycle Analysis. VSD investigators developed an internal dashboard to facilitate visualization and rapid reviews of large weekly automated vaccine safety surveillance data. Dashboard development and maintenance was informed by vaccine surveillance data users and vaccine safety partners. Key metrics include population demographics, vaccine uptake, pre-specified safety outcomes, sequential analyses results, and descriptive data on potential vaccine safety signals. Dashboard visualizations are used to provide situational awareness on dynamic vaccination coverage and the status of multiple safety analyses conducted among the VSD population. This report describes the development and implementation of the internal VSD COVID-19 Vaccine Dashboard, including metrics used to develop the dashboard, which may have application across various other public health settings.

Effectiveness of Homologous and Heterologous COVID-19 Booster Doses Following 1 Ad.26.COV2.S (Janssen [Johnson & Johnson]) Vaccine Dose Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults - VISION Network, 10 States, December 2021-March 2022.

CDC recommends that all persons aged ≥18 years receive a single COVID-19 vaccine booster dose ≥2 months after receipt of an Ad.26.COV2.S (Janssen [Johnson & Johnson]) adenovirus vector-based primary series vaccine; a heterologous COVID-19 mRNA vaccine is preferred over a homologous (matching) Janssen vaccine for booster vaccination. This recommendation was made in light of the risks for rare but serious adverse events following receipt of a Janssen vaccine, including thrombosis with thrombocytopenia syndrome and Guillain-Barré syndrome† (1), and clinical trial data indicating similar or higher neutralizing antibody response following heterologous boosting compared with homologous boosting (2). Data on real-world vaccine effectiveness (VE) of different booster strategies following a primary Janssen vaccine dose are limited, particularly during the period of Omicron variant predominance. The VISION Network§ determined real-world VE of 1 Janssen vaccine dose and 2 alternative booster dose strategies: 1) a homologous booster (i.e., 2 Janssen doses) and 2) a heterologous mRNA booster (i.e., 1 Janssen dose/1 mRNA dose). In addition, VE of these booster strategies was compared with VE of a homologous booster following mRNA primary series vaccination (i.e., 3 mRNA doses). The study examined 80,287 emergency department/urgent care (ED/UC) visits¶ and 25,244 hospitalizations across 10 states during December 16, 2021-March 7, 2022, when Omicron was the predominant circulating variant.** VE against laboratory-confirmed COVID-19-associated ED/UC encounters was 24% after 1 Janssen dose, 54% after 2 Janssen doses, 79% after 1 Janssen/1 mRNA dose, and 83% after 3 mRNA doses. VE for the same vaccination strategies against laboratory-confirmed COVID-19-associated hospitalizations were 31%, 67%, 78%, and 90%, respectively. All booster strategies provided higher protection than a single Janssen dose against ED/UC visits and hospitalizations during Omicron variant predominance. Vaccination with 1 Janssen/1 mRNA dose provided higher protection than did 2 Janssen doses against COVID-19-associated ED/UC visits and was comparable to protection provided by 3 mRNA doses during the first 120 days after a booster dose. However, 3 mRNA doses provided higher protection against COVID-19-associated hospitalizations than did other booster strategies during the same time interval since booster dose. All adults who have received mRNA vaccines for their COVID-19 primary series vaccination should receive an mRNA booster dose when eligible. Adults who received a primary Janssen vaccine dose should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later, or a homologous Janssen vaccine booster dose if mRNA vaccine is contraindicated or unavailable. Further investigation of the durability of protection afforded by different booster strategies is warranted.